Abstract
Presentation Description :
Dysregulation of extracellular matrix (ECM) homeostasis in the conventional outflow pathway results in elevated IOP. A prominent player involved in ECM dysregulation is a subset of extracellular vesicles (EVs) known as exosomes. Exosome release from cells is tightly regulated, and they are differentiated from other nanovesicles based on their smaller size, cell type-specific cargo, and thus function. Our hypothesis is that exosomes released from TM cells target ECM components for opsonization to facilitate ECM homeostasis in outflow tissues. To test our hypothesis, we compared exosome cargo/binding proteins released from glaucomatous versus non-glaucomatous TM cells. We found distinct differences in ECM-related proteins between non-glaucoma and glaucoma exosomes; specifically the expression of fibronectin, and proteins that bind fibronectin – integrin β3, EGF like repeats and Discoidin I-like domains 3 (EDIL3). Further, when we examined the molecular function of the protein cargo of TM exosomes, we found differences in specific ECM-related pathways such as ECM and cytoskeleton structural components between the glaucomatous and non-glaucomatous exosomes. Together, data indicate that exosomes play a role in ECM turnover in response to IOP which is compromised in diseased TM cells, supporting the hypothesis that exosomes facilitate ECM turnover by binding ECM proteins for degradation.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.